1. Field of the Invention
The present invention relates to an improved and industrially advantageous method for preparing atomoxetine.
2. Description of Related Art
(R)-(−)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine (Atomoxetine®) is used for treating attention-deficit hyperactivity disorder (ADHD). It is twice as effective as the racemate and nine times more effective than the (S)-enantiomer.

There have been several methods reported for preparing (R)-(−)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine (Atomoxetine®). For example, U.S. Pat. No. 4,868,344 discloses a process as shown in the following scheme:
In this example, 3-chloropropiophenone is used as the starting material to be asymmetrically reduced with (−)-diisopinocamphenylchloroborane ((−)-IPc2BC1) to give the corresponding chiral alcohol. The resulting chiral alcohol is then reacted with o-cresol via Mitsunobu reaction to form the chiral ether compound. Subsequently, amination of the chiral ether compound with methylamine provided atomoxetine. In this process, the materials such as chiral-borane ((−)-IPc2BC1) and diethyl azodicarboxylate (DEAD) are expensive, and result in high manufacturing cost.
Further, WO 2006/009884 discloses another method for preparing atomoxetine, including the step of reacting N-methyl-3-phenyl-3-hydroxypropylamine with 2-fluorotoluene which is followed by resolution of the resulting product to provide optically pure atomoxetine as shown in the following scheme:

This process involving a chiral resolution step is inefficient due to low product yield, complicated and long time process that renders this process economically less competitive.
Accordingly, the present invention provide a novel method for preparing atomoxetine to overcome the drawbacks of the conventional methods.